We have previously identified and isolated unesterified cholesterol-rich particles that accumulate in the extracellular space of human atherosclerotic lesions. HDL is the major lipoprotein class thought to be involved in transporting cholesterol from peripheral tissues to the liver for reutilization or excretion. The purpose of this project is to determine whether and by what mechanism human high density lipoprotein (HDL) can solubilize these unesterified cholesterol-rich lipid particles. In order to study the interaction between aortic unesterified cholesterol-rich particles (diameter = 1000 Angstroms) and HDL (diameter = 100 A), we incubated the aortic particles with HDL and studied the morphological changes in these particles. As a result of incubation, a new intermediate sized particle appeared with a modal diameter of 180-200 Angstroms (size range between 150-250 A). These new lipid particles surrounded the larger aortic particles or occupied the entire domain of the aortic particles. This suggested that HDLs transformed the large aortic particles into smaller intermediate sized particles or that HDLs served as cholesterol acceptors effectively solubilizing cholesterol from the aortic particles. With solubilization of cholesterol, HDL transformed into an enlarged cholesterol-rich HDL. Unesterified cholesterol-rich lipid particles have been shown to be an important early event in the development of atherosclerotic lesions. Removing these particles from the atherosclerotic lesion, therefore, could be a way to reduce the atherosclerosis process. Our preliminary findings suggest that plasma HDL may contribute to the removal of these atherosclerotic plaque lipid particles. Further investigation concerning mechanisms of this reaction may help elucidate ways to enhance lipid removal from atherosclerotic lesions.